Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma.

This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

The role of para-aortic lymphadenectomy in stage IIIC endometrial cancer: A single-institute study.

The therapeutic value of para-aortic lymphadenectomy (PAL) in women with endometrial cancer (EC) remains uncertain. We retrospectively analysed 25 patients with stage IIIc EC (17 stage IIIC1; 8 IIIC2) who were treated in our institution. All subjects had undergone pelvic lymphadenectomies in which para-aortic nodes were sampled, or removed only when these nodes were enlarged. Sampling of para-aortic nodes or PAL was performed in all patients with stage IIIC2 disease and one of 17 with stage IIIC1 disease. Para-aortic lymph nodes were the most frequent site of recurrence in stage IIIC1 patients, but no such recurrences occurred in stage IIIC2 patients. Overall survival tended to be shorter in stage IIIC1 patients than stage IIIC2 patients. Our findings indicate that PAL improves the outcomes of patients with EC and high risk of para-aortic lymph node metastasis, such as those with positive pelvic lymph nodes or enlargement of para-aortic lymph nodes. Impact statement Para-aortic lymph node (PALN) metastases are important prognostic factors in endometrial cancer. Overall survival of patients with stage IIIC1 disease is generally longer than for those with stage IIIC2 disease. Retrospective studies - but no prospective studies - have suggested that para-aortic lymphadenectomy (PAL) provides a survival benefit. In our institution, we had performed PAL or para-aortic sampling for patients with enlarged PALNs; therefore, as most IIIC1 patients had no enlarged PALNs, they underwent pelvic lymphadenectomy only, whereas all IIIC2 patients had enlarged PALNs and underwent pelvic lymphadenectomy and PAL or PALN sampling in addition to pelvic lymphadenectomy. However, under this policy, survival of stage IIIC1 patients was not better than for stage IIIC2 patients. Our retrospective study indicates a survival benefit for PAL in patients with pelvic node-positive or enlarged PALN. PAL warrants a prospective randomised trial to see whether it should be a standard treatment in these patients.

Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A).

OBJECTIVE: In order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter≤2 cm were investigated. METHODS: We conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2 cm or less (cT≤2 cm) and ii) greater than 2 cm (cT>2 cm). We expected 5-year OS of ≥95% and parametrial involvement<2-3% for patients with cT≤2 cm who underwent radical hysterectomy. RESULTS: Of the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2 cm and 248 with cT>2 cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2 cm and 12.9% (32/248) with cT>2 cm. Five-year overall survivals were 95.8% (95% CI 92.9-97.6%) in cT≤2 cm and 91.9% (95% CI 87.6-94.8%) in cT>2 cm patients. CONCLUSION: Patients with cT≤2 cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery.

A phase II study of paclitaxel and carboplatin with a biweekly schedule in patients with epithelial ovarian cancer: Gynecologic Cancer Network trial.

AIM: The objective of this multicenter phase II study was to evaluate the effects of biweekly paclitaxel and carboplatin combination chemotherapy on response rate and toxicities in patients with epithelial ovarian cancer. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage II to IV ovarian cancer received paclitaxel at a dose of 120 mg/m(2) and carboplatin at an area under the curve of 3 mg/mL per minute every 2 weeks for 8 or more cycles. Inclusion criteria included an Eastern Cooperative Oncology Group performance status of 0 to 2 and no previous chemotherapy. Informed consent was obtained from each patient before the start of treatment. RESULTS: From March 2003 through July 2009, 42 patients from 5 institutions were eligible to be evaluated for response and toxicity. The median age was 60.5 years (age range, 34-81 years). The International Federation of Gynecology and Obstetrics stage was stage II in 3 patients, stage III in 31 patients, and stage IV in 8 patients. The response rate was 66.7% (95% confidence interval: 50.5%-80.4%). Sixty-nine percent (29 of 42) of patients received 8 or more cycles of chemotherapy. The median progression-free survival was 18.5 months, and overall survival was 59.1 months. The most common grade 3 or 4 hematological toxicity was neutropenia (61.0%). No patients had grade 3 or 4 thrombocytopenia. The most common grade 3 nonhematological toxicities were neuropathy (4.9%) and nausea (2.4%). CONCLUSION: Paclitaxel combined with carboplatin using a biweekly schedule is a safe and effective chemotherapy regimen for patients with epithelial ovarian cancer. Our results suggest that a biweekly schedule is well tolerated and is less toxic than a triweekly schedule.

Conservative treatment of stage IA1 adenocarcinoma of the uterine cervix with a long-term follow-up.

OBJECTIVES: The adenocarcinoma of the uterine cervix tends to arise in women of childbearing age. Conservative treatment by conization is an alternative to a hysterectomy that allows future pregnancy; however, much less is known about the management of adenocarcinoma because of its rarity and relatively short time frame of follow-up. The purpose of this study was to determine the long-term outcome of patients treated by conization alone. METHODS: All patients diagnosed to have FIGO (International Federation of Gynecology and Obstetrics) stage IA1 cervical adenocarcinoma between 1990 and 2004 with more than 5 years' follow-up at 2 institutions were reviewed. Information was abstracted on clinical data including margin status of conization and recurrence. RESULTS: Twenty-seven patients were identified, and 10 patients who expressed a strong desire to preserve fertility were offered a conization and careful surveillance without hysterectomy. The median age was 35 years, and 40% were nulliparous. All tumors were endocervical-type adenocarcinoma, and all tumors were grade 1. None had lymphovascular space invasion. Two patients had a repeated conization because of a positive margin. No recurrence was observed during an average follow-up of 75 months. CONCLUSIONS: Although further studies on the management of microinvasive cervical adenocarcinoma are desirable, conization seems to be acceptable treatment modality for patients with stage IA1 cervical adenocarcinoma who desire to preserve their fertility. A careful and long-term follow-up is needed because of lack of sufficient evidence for the safety of this treatment.

Origin of adenocarcinoma cells observed on cervical cytology.

OBJECTIVE: To clarify the ratio of diseases suspected when malignant glandular cells are observed on cervical cytology. STUDY DESIGN: Seventy cases of cervical adenocarcinoma/adenosquamous carcinoma, 207 cases of endometrial adenocarcinoma, 7 cases of tubal adenocarcinoma and 83 cases of ovarian adenocarcinoma were reviewed. The positive rate in cervical cytology performed 3 months before surgery was calculated. Based on the positive rate for each entity and the number of cases treated in the previous 10 years, we estimated the incidence of disease responsible for malignant glandular cells on cytology. RESULTS: The positive rate was 93% in cervical adenocarcinoma/adenosquamous carcinoma, 45% in endometrial adenocarcinoma, 14% in tubal adenocarcinoma and 6% in ovarian adenocarcinoma. These positive rates and case numbers at our institute indicated the percentage of suspicious diseases to be 38% for cervical aaenocarcinoma/adenosquamous carcinoma, 53% for endometrial adenocarcinoma, 1% for tubal adenocarcinoma and 8% for ovarian adenocarcinoma. CONCLUSION: When a cytologic specimen suggested the existence of adenocarcinoma, the most probable disease was endometrial adenocarcinoma, and the second was cervical adenocarcinoma/adenosquamous carcinoma. Adnexal malignancies were responsible in 9% of cases. In the case of positive cervical cytology suggesting adenocarcinoma, the ratio of suspicious diseases is as valuable as the cytologic findings for the differential diagnosis.